7DQ7

Cryo-EM structure of Coxsackievirus B1 mature virion in complex with nAb 5F5

Summary for 7DQ7

• Entry DOI: 10.2210/pdb7dq7/pdb
• EMDB information: 30815
• Descriptor: Virion protein 1, VP2, VP3, ... (7 entities in total)
• Functional Keywords: coxsackievirus b1, car, cryo-em, neutralizing antibody, virus, virus-immune system complex, virus/immune system
• Biological source: Coxsackievirus B1; More
• Total number of polymer chains: 6
• Total formula weight: 119381.04

Authors

Li, S.,Zhu, R.,Xu, L.,Cheng, T.,Zheng, Q. (deposition date: 2020-12-22, release date: 2021-05-05)

Primary citation

Xu, L.,Zheng, Q.,Zhu, R.,Yin, Z.,Yu, H.,Lin, Y.,Wu, Y.,He, M.,Huang, Y.,Jiang, Y.,Sun, H.,Zha, Z.,Yang, H.,Huang, Q.,Zhang, D.,Chen, Z.,Ye, X.,Han, J.,Yang, L.,Liu, C.,Que, Y.,Fang, M.,Gu, Y.,Zhang, J.,Luo, W.,Zhou, Z.H.,Li, S.,Cheng, T.,Xia, N.
Cryo-EM structures reveal the molecular basis of receptor-initiated coxsackievirus uncoating.
Cell Host Microbe, 29:448-462.e5, 2021

PubMed Abstract: Enterovirus uncoating receptors bind at the surface depression ("canyon") that encircles each capsid vertex causing the release of a host-derived lipid called "pocket factor" that is buried in a hydrophobic pocket formed by the major viral capsid protein, VP1. Coxsackievirus and adenovirus receptor (CAR) is a universal uncoating receptor of group B coxsackieviruses (CVB). Here, we present five high-resolution cryoEM structures of CVB representing different stages of virus infection. Structural comparisons show that the CAR penetrates deeper into the canyon than other uncoating receptors, leading to a cascade of events: collapse of the VP1 hydrophobic pocket, high-efficiency release of the pocket factor and viral uncoating and genome release under neutral pH, as compared with low pH. Furthermore, we identified a potent therapeutic antibody that can neutralize viral infection by interfering with virion-CAR interactions, destabilizing the capsid and inducing virion disruption. Together, these results define the structural basis of CVB cell entry and antibody neutralization.

PubMed: 33539764
DOI: 10.1016/j.chom.2021.01.001

Experimental method

ELECTRON MICROSCOPY (3.2 Å)